2-Decarboxy-2-hydroxymethyl-13,14-didehydro-17-phenyl-PGA, PGD and PGE compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl is replaced by a primary alcohol and the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostanglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 814,410, filed July 11, 1977, now pending, which application is a divisional application of Ser. No. 708,752, filed July 26, 1976, issued as U.S. Pat. No. 4,058,564 on Nov. 15, 1977.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,058,564, issued Nov. 15, 1977. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## WHEREIN ##STR2## wherein R₈ is hydrogen or hydroxy; WHEREIN M₁ is ##STR3## wherein R₅ is hydrogen or methyl; WHEREIN L₁ is ##STR4## or a mixture of ##STR5## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is methyl only when the other is hydrogen or methyl;Wherein Z₁₀ is (1) cis--CH═CH--CH--(CH₂)_(g) --CH₂ --, (2) cis-- CH═CH--CH₂ --(CH₂)_(g) --CF₂ --,(3) cis--CH₂ --CH═CH--(CH₂)_(g) -CH₂ --, (4) --(ch₂)₃ --(ch₂)_(g) --CH₂ --, (5) --(ch₂)₃ --(ch₂)_(g) --CF₂ --, or (6) --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --,wherein g is one, 2, or 3; and wherein s is one to 3, inclusive and T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, the various T's being the same or different, with the proviso that not more than two are other than alkyl.
 2. A prostaglandin analog according to claim 1, wherein D is ##STR6##
 3. A prostaglandin analog according to claim 2, wherein R₈ is hydrogen.
 4. A prostaglandin analog according to claim 2, wherein R₈ is hydroxy.
 5. A prostaglandin analog according to claim 1, wherein D is ##STR7##
 6. A prostaglandin analog according to claim 1, wherein D is ##STR8##
 7. A prostaglandin analog according to claim 1, wherein D is ##STR9##
 8. A prostaglandin analog according to claim 7, wherein Z₁₀ is cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 9. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 8. 10. A prostaglandin analog to claim 7, wherein Z₁₀ is --(CH₂)₃ --(CH₂)g--CF₂ --.
 11. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostglandin analog according to claim
 10. 12. A prostaglandin analog according to claim 7, wherein Z₁₀ is cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 13. 2-Decarboxy-2-hydroxymethyl-cis-4,5didehydro-13,14-didehydro-17-phenyl 18,19,20-trinor-PGE₁, a prostaglandin according to claim
 12. 14. A prostaglandin analog according to claim 7, wherein Z₁₀ is --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --.
 15. 2-Decarboxy-2-hydroxymethyl-5-oxa-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostglandin analog according to claim
 14. 16. A prostaglandin analog according to claim 7, wherein Z₁₀ is --(CH₂)₃ --(CH₂)_(g) --CH₂ --.
 17. A prostaglandin analog according to claim 16, wherein M₁ is ##STR10##
 18. 2-Decarboxy-2-hydroxymethyl-15-epi-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 17. 19. A prostaglandin analog according to claim 16, wherein M₁ is ##STR11##
 20. A prostaglandin analog according to claim 19, wherein m is
 3. 21. A prostaglandin analog according to claim 20, wherein g is
 3. 22. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-methyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 21. 23. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 21. 24. A prostaglandin analog according to claim 20, wherein g is
 1. 25. A prostaglandin analog according to claim 24, wherein at least one of R₃ and R₄ is methyl.
 26. A prostaglandin analog according to claim 25, wherein R₃ and R₄ are both methyl.
 27. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 26. 28. A prostaglandin analog according to claim 27, wherein at least two of R₃, R₄, and R₅ are methyl.
 29. A prostaglandin analog according to claim 28, wherein R₃, R₄, and R₅ are all methyl.
 30. 2-Decarboxy-2-hydroxymethyl-15,16,16-trimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 29. 31. A prostaglandin analog according to claim 24, wherein R₃ and R₄ are both hydrogen.
 32. A prostaglandin analog according to claim 31, wherein R₅ is methyl.
 33. 2-Decarboxy-2-hydroxymethyl-15-methyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 31. 34. A prostaglandin analog according to claim 31, wherein R₅ is hydrogen.
 35. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₁, a prostaglandin analog according to claim
 34. 36. A prostaglandin analog according to claim 7, wherein Z₁₀ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 37. A prostaglandin analog according to claim 36, wherein M₁ is ##STR12##
 38. A prostaglandin analog according to claim 37, wherein m is
 3. 39. A prostaglandin analog according to claim 38, wherein g is
 3. 40. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-epi-15-methyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 39. 41. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-epi-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE.sub.2, a prostaglandin analog according to claim
 39. 42. A prostaglandin analog according to claim 38, wherein g is
 1. 43. A prostaglandin analog according to claim 42, wherein at least one of R₃ and R₄ is methyl.
 44. 2-Decarboxy-2-hydroxymethyl-15-epi-13,14-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 43. 45. A prostaglandin analog according to claim 42, wherein at least two of R₃, R₄, and R₅ are methyl.
 46. 2-Decarboxy-2-hydroxymethyl-15-epi-15,16,16-trimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 40. 47. A prostaglandin analog according to claim 42, wherein R₃ and R₄ are both hydrogen.
 48. 2-Decarboxy-2-hydroxymethyl-15-epi-15-methyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 47. 49. A prostaglandin analog according to claim 36, wherein M₁ is ##STR13##
 50. A prostaglandin analog according to claim 49, wherein m is
 3. 51. A prostaglandin analog according to claim 50, wherein g is
 3. 52. A prostaglandin analog according to claim 51, wherein at least one of R₃ and R₄ is methyl.
 53. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-16,16-dimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE.sub.2, a prostaglandin analog according to claim
 52. 54. A prostaglandin analog according to claim 51, wherein at least two of R₃, R₄, and R₅ are methyl.
 55. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15,16,16-trimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 54. 56. A prostaglandin analog according to claim 51, wherein R₃ and R₄ are both hydrogen.
 57. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-methyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE.sub. 2, a prostaglandin analog according to claim
 56. 58. A prostaglandin analog according to claim 50, wherein g is
 1. 59. A prostaglandin analog according to claim 58, wherein at least one of R₃ and R₄ is methyl.
 60. A prostaglandin analog according to claim 59, wherein only one of R₃ and R₄ is methyl.
 61. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-16-methyl-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 60. 62. A prostaglandin analog according to claim 59, wherein R₃ and R₄ are both methyl.
 63. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 62. 64. A prostaglandin analog according to claim 58, wherein at least one of R₃ and R₄ is fluoro.
 65. A prostaglandin analog according to claim 64, wherein R₃ and R₄ are both fluoro.
 66. A prostaglandin analog according to claim 65, wherein R₅ is methyl.
 67. 2-Decarboxy-2-hydroxymethyl-15-methyl- 16,16-difluoro-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 66. 68. A prostaglandin analog according to claim 65, wherein R₅ is hydrogen.
 69. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 68. 70. A prostaglandin analog according to claim 58, wherein R₃ and R₄ are both hydrogen.
 71. A prostaglandin analog according to claim 70, wherein R₅ is methyl.
 72. 2-Decarboxy-2-hydroxymethyl-15-methyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 71. 73. A prostaglandin analog according to claim 70, wherein R₅ is hydrogen.
 74. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGE₂, a prostaglandin analog according to claim
 73. 